Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells

免疫突触指导树突状细胞的表观基因组和转录组功能重编程

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作者:Ana Alcaraz-Serna ,Eugenio Bustos-Morán ,Irene Fernández-Delgado ,Diego Calzada-Fraile ,Daniel Torralba ,Ester Marina-Zárate ,Erika Lorenzo-Vivas ,Enrique Vázquez ,Juliana Barreto de Albuquerque ,Nora Ruef ,Manuel José Gómez ,Fátima Sánchez-Cabo ,Ana Dopazo ,Jens V Stein ,Almudena Ramiro ,Francisco Sánchez-Madrid

Abstract

Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells.

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